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Biological sex differences exist for many airway diseases in which females have either worse or better health outcomes. Inflammatory airway diseases such as cystic fibrosis (CF) and asthma display a clear male advantage in post-puberty while a female benefit is observed in asthma during the pre-puberty years. The influence of menstrual cycle stage and pregnancy on the frequency and severity of pulmonary exacerbations in CF and asthma point to a role for sex steroid hormones, particularly estrogen, in underpinning biological sex differences in these diseases. There are many ways by which estrogen may aggravate asthma and CF involving disturbances in airway surface liquid (ASL) dynamics, inappropriate hyper-immune and allergenic responses, as well as exacerbation of pathogen virulence. The deleterious effect of estrogen on pulmonary function in CF and asthma contrasts with the female advantage observed in airway diseases characterised by pulmonary edema such as pneumonia, acute respiratory distress syndrome (ARDS) and COVID-19. Airway surface liquid hypersecretion and alveolar flooding are hallmarks of ARDS and COVID-19, and contribute to the morbidity and mortality of severe forms of these diseases. ASL dynamics encompasses the intrinsic features of the thin lining of fluid covering the airway epithelium which regulate mucociliary clearance (ciliary beat, ASL height, volume, pH, viscosity, mucins, and channel activating proteases) in addition to innate defence mechanisms (pathogen virulence, cytokines, defensins, specialised pro-resolution lipid mediators, and metabolism). Estrogen regulation of ASL dynamics contributing to biological sex differences in CF, asthma and COVID-19 is a major focus of this review. Plain Language Summary: Sex differences exist in many airway diseases in which females have either worse or better health outcomes. These include cystic fibrosis (CF) and asthma where females post-puberty have more frequent lung exacerbations and higher mortality. Lung infections and difficulty in breathing become worse in post-puberty in females and during the ovulation period of the menstrual cycle, and in pregnancy, indicating a role for sex hormones in underpinning sex differences in CF and asthma. Evidence also exists for sex differences with a female advantage in airway diseases which are characterised by flooding of the airways, as in pneumonia and COVID-19, where females have better lung function and lower risk of death than males. The female sex hormone estrogen plays an important role in determining the role of sex biology in airway disease severity and mortality. Estrogen can control the movement of salt and water in and out of the lung airway tubes and dehydrate the lung surface to make it more sticky with mucus, as observed in CF and asthma, thus worsening the condition. In contrast, estrogen can have beneficial effects in lowering the volume of water in the lungs in COVID-19 thus alleviating flooding of the airways. This review focusses on the biology of sex differences in CF, asthma and COVID-19, and the cellular mechanisms by which estrogen can have either detrimental or beneficial effects in these diseases. Highlights: Airway diseases such as cystic fibrosis (CF), asthma and COVID-19 show marked sex differences in their morbidity and mortality Estrogen and female sex are associated with exacerbated CF and asthma Estrogen aggravates CF and asthma by compromising the optimal airway surface liquid dynamics for effective mucociliary clearance and by exacerbating bacterial virulence Estrogen confers a female advantage in COVID-19 by reducing airway flooding and reinforcing immunity. [ABSTRACT FROM AUTHOR]

We investigated 17 metrics derived from four leads of electrocardiographic (ECG) signals from hospital patient monitors to develop new ECG alarms for predicting adult bradyasystolic cardiac arrest events.A retrospective case-control study was designed to analyze 17 ECG metrics from 27 adult bradyasystolic and 304 control patients. The 17 metrics consisted of PR interval (PR), P-wave duration (Pdur), QRS duration (QRSdur), RR interval (RR), QT interval (QT), estimate of serum K  +  using only frontal leads (SerumK2), T-wave complexity (T Complex), ST segment levels for leads I, II, V (ST I, ST II, ST V), and 7 heart rate variability (HRV) metrics. These 7 HRV metrics were standard deviation of normal to normal intervals (SDNN), total power, very low frequency power, low frequency power, high frequency power, normalized low frequency power, and normalized high frequency power. Controls were matched by gender, age (±5 years), admission to the same hospital unit within the same month, and the same major diagnostic category. A research ECG analysis software program developed by co-author D M was used to automatically extract the metrics. The absolute value for each ECG metric, and the duration, terminal value, and slope of the dominant trend for each ECG metric, were derived and tested as the alarm conditions. The maximal true positive rate (TPR) of detecting cardiac arrest at a prescribed maximal false positive rate (FPR) based on the trending conditions was reported. Lead time was also recorded as the time between the first time alarm condition was triggered and the event of cardiac arrest.While conditions based on the absolute values of ECG metrics do not provide discriminative information to predict bradyasystolic cardiac arrest, the trending conditions can be useful. For example, with a max FPR  =  5.0%, some derived alarms conditions are: trend duration of PR  >  2.8 h (TPR  =  48.2%, lead time  =  10.0  ±  6.6 h), trend duration of QRSdur  >  2.7 h (TPR  =  40.7%, lead time  =  8.8  ±  6.2 h), trend duration of RR  >  3.5 h (TPR  =  51.9%, lead time  =  6.4  ±  5.5 h), trend duration of T Complex  >  2.9 h (TPR  =  40.7%, lead time  =  6.8  ±  5.5 h), trend duration of ST I  >  3.0 h (TPR of 51.9%, lead time  =  8.4  ±  8.0 h), trend duration of SDNN  >  3.6 h (TPR of 40.7%, lead time  =  11.0  ±  8.6 h), trend duration of HRV total power  >  3.0 h (TPR of 25.9%, lead time  =  7.5  ±  8.1 h), terminal value of ST I    19.4 ms h(-1) (TPR  =  25.9%, lead time  =  6.7  ±  6.9 h). Eleven trend duration alarms, eight terminal value alarms, and ten slope alarms, achieved a positive TPR with zero FPR. Furthermore, these alarms conditions with zero PFR can be combined by the 'OR'logic could further improve the TPR without increasing the FPR.The trend duration, terminal value, and slope of the dominant trend of the ECG metrics considered in this study are able to predict a subset of patients with bradyasystolic cardiac arrests with low or even zero FPR, which can be used for developing new ECG alarms.

An age-structured, spatial survey-based assessment model (SSURBA) is developed and applied to the Grand Banks stock (NAFO Divisions 3LNO) of American plaice (Hippoglossoides platessoides) in Newfoundland and Labrador. The state-space model is fit to annual spatial (i.e., three divisions) stock size-at-age research vessel (RV) survey indices that are assumed to be proportional to abundance. We model index catchability (q) as a logistic function of fish length, which varies with age, cohort, and the time of the survey; therefore, the model facilitates the estimation of q values that change spatially and temporally following changes in fish growth and survey gears. The SSURBA model produces division-level estimates of fishing mortality rates (F), stock productivity, and stock size relative to the logistic catchability assumption with q = 1 for fully selected ages. The spatial model allows us to include additional survey information compared with the space-aggregated assessment model (all of 3LNO) that is currently used to assess stock status. The model can provide estimates of relative catch, which we compare with reported catch trends to partially validate the model. Un modele devaluation base sur des releves spatiaux structures par age (SSURBA) est mis au point et utilise pour le stock des Grands Bancs (divisions 3LNO de l'OPANO) de plies canadiennes (Hippoglossoidesplatessoides) a Terre-Neuve-et- Labrador. Le modele d'espace d'etats est cale sur des indices de releves par navire de recherche (NR) de l'age selon la taille du stock qui sont presumes proportionnels a l'abondance. Nous modelisons la capturabilite indexee (q) en tant que fonction logistique de la longueur des poissons, qui varie selon l'age, la cohorte et le moment du releve; ainsi le modele facilite l'estimation de q qui varient dans l'espace et le temps a la suite de changements de la croissance des poissons et des engins utilises pour les releves. Le modele SSURBA produit des estimations au niveau de la division des taux de mortalite par peche (F), de la productivite du stock et de la taille du stock au vu de l'hypothese de capturabilite logistique pour q = 1 pour des ages entierement selectionnes. Le modele spatial nous permet d'inclure plus d'information tiree des releves que ce que permet le modele devaluation spatialement regroupe (ensemble des 3LNO) actuellement utilise pour evaluer l'etat du stock. Le modele peut fournir des estimations des prises relatives que nous comparons aux tendances des prises rapportees afin de valider partiellement le modele. [Traduit par la Redaction], Introduction Canadian fisheries management has a long history of conducting scientific surveys to monitor fish populations, with some of the earliest surveys dating back to the 1970s (Halliday and Fanning [...]

Juvenile mortality is an important factor affecting the spatiotemporal dynamics of fish recruitment, but estimation of the spatiotemporal variations in juvenile mortality rates remains challenging. We developed a state-space metapopulation dynamics model to simultaneously estimate spatiotemporal variations in juvenile mortality rates and cohort strength and applied this general modelling framework to data from multiple surveys for juvenile (ages 2-5) Atlantic cod (Gadus morhua) stocks off Newfoundland and Labrador (NL). We found large-scale synchronized dynamics of decreasing juvenile mortality rates and increasing cohort strength from offshore surveys off eastern and southeastern NL, suggesting improving reproduction and survival rates for juvenile cod. No synchronized patterns of juvenile mortality rates and cohort strength were detected for cod stocks off southern and western NL, indicating more complex cod population spatial structures in those areas. Our study demonstrates the potential of juvenile mortality to cause temporally variable and spatially synchronized dynamics of fish recruitment, and the spatial patterns of juvenile mortality and cohort strength indicate some potential mismatch between cod population structure and current management units off NL. Si la mortalite juvenile est un important facteur agissant sur la dynamique spatiotemporelle du recrutement de poissons, l'estimation des variations spatiotemporelles des taux de mortalite juvenile demeure difficile. Nous avons mis au point un modele d'espace d'etats de la dynamique de la metapopulation pour estimer simultanement les variations spatiotemporelles des taux de mortalite juvenile et de l'abondance des cohortes et avons applique ce cadre de modelisation general aux donnees de plusieurs evaluations portant sur des stocks de morues (Gadus morhua) juveniles (de 2 a 5 ans) au large de Terre- Neuve-etLabrador (T.-N.-L.). Nous relevons une dynamique synchronisee a grande echelle de diminution des taux de mortalite juvenile et d'augmentation de l'abondance des cohortes pour les evaluations au large de l'est et du sud-est de T.-N.-L., ce qui indiquerait une amelioration de la reproduction et des taux de survie des morues juveniles. Aucun motif synchronise des taux de mortalite juvenile et de l'abondance des cohortes n'est decele pour les stocks de morues au large du sud et de l'ouest de T.-N.- L., ce qui temoigne de structures spatiales plus complexes des populations de morues dans ces secteurs. L'etude demontre que la mortalite juvenile pourrait causer une dynamique variable dans le temps et synchronisee dans l'espace du recrutement de poissons, et les motifs spatiaux de mortalite juvenile et d'abondance des cohortes indiquent un mesappariement potentiel entre la structure des populations de morues et les unites de gestion actuelles au large de T.-N.-L. [Traduit par la Redaction], Introduction Two intriguing patterns of fish recruitment are strong temporal variation and large-scale spatial synchronization (e.g., Myers et al. 1997; Houde 2008), and understanding the spatiotemporal dynamics of fish recruitment [...]

Response-selective stratified sampling (RSSS) has been well studied in the statistical literature; however, the application of the resulting statistical theories and methods to a specific case of RSSS in fisheries studies, namely length- stratified age sampling (LSAS), is inadequate. We review nine estimation approaches for RSSS found in the statistical and fisheries science literature in terms of three sampling components: the first phase length composition sample, the second phase age composition sample, and the sampling scheme. We compare the performance in terms of RRMSE (relative root mean squared error) for von Bertalanffy (vonB) growth model parameter estimation using an extensive simulation study. We further demonstrate methods by applying the two best-performing and the most popular methods to estimate the vonB model parameters for American plaice (Hippoglossoides platessoides) in NAFO Divisions 3LNO. Our simulations demonstrated that mis-specifying one or more of the three sampling components increases the RRMSEs, and this effect is magnified when the age distribution is incorrectly specified. The optimal approach for data based on LSAS is the empirical proportion approach, and we recommend this method for growth parameter estimation based on LSAS data. L'echantillonnage stratifie a selectivity basee sur la reponse (ESSR) est un sujet bien etudie dans la documentation statistique, mais l'application des theories et methodes statistiques en decoulant a un cas precis d'ESSR dans les etudes sur les peches, a savoir l'echantillonnage d'ages stratifie selon la longueur (EASL), est inadequate. Nous passons en revue neuf approches d'estimation pour l'ESSR relevees dans la documentation statistique et sur les sciences halieutiques au vu de trois composants de l'echantillonnage, soit l'echantillon de la composition des longueurs de la premiere phase, l'echantillon de la composition des ages de la deuxieme phase et le plan d'echantillonnage. Nous en comparons la performance a la lumiere de l'erreur quadratique moyenne relative (EQMR) pour l'estimation des parametres du modele de croissance de von Bertalanffy (vonB) en utilisant une vaste etude de simulation. Nous faisons en outre la demonstration de methodes en appliquant les deux methodes les plus performantes et les methodes les plus populaires pour estimer les parametres du modele vonB pour la plie canadienne (Hippoglossoides platessoides) dans les divisions 3LNO de l'OPANO. Nos simulations demontrent que la definition erronee d'au moins un des trois composants de l'echantillonnage accroit les EQMR, et cet effet est amplifie si la repartition des ages est definie incorrectement. L'approche optimale pour des donnees basees sur l'EASL est l'approche des proportions empiriques, et nous recommandons cette methode pour l'estimation des parametres de croissance basee sur des donnees d'EASL. [Traduit par la Redaction], Introduction Modeling and estimation of the relationship between fish length and age (i.e., growth) is an important component of fisheries science. Growth models are used in many ways, including the [...]

Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ɛ4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ɛ4 being the major genetic risk factor for AD.

BackgroundIt is not known whether the most delayed late potentials are functionally most specific for scar-related ventricular tachycardia (VT) circuits.Methods and resultsIsochronal late activation maps were constructed to display ventricular activation during sinus rhythm over 8 isochrones. Analysis was performed at successful VT termination sites and prospectively tested. Thirty-three patients with 47 scar-related VTs where a critical site was demonstrated by termination of VT during ablation were retrospectively analyzed. In those who underwent mapping of multiple surfaces, 90% of critical sites were on the surface that contained the latest late potential. However, only 11% of critical sites were localized to the latest isochrone (87.5%-100%) of ventricular activation. The median percentage of latest activation at critical sites was 78% at a distance from the latest isochrone of 18 mm. Sites critical to reentry were harbored in regions with slow conduction velocity, where 3 isochrones were present within a 1-cm radius. Ten consecutive patients underwent ablation prospectively guided by isochronal late activation maps, targeting concentric isochrones outside of the latest isochrone. Elimination of the targeted VT was achieved in 90%. Termination of VT was achieved in 6 patients at a mean ventricular activation percentage of 78%, with only 1 requiring ablation in the latest isochrone.ConclusionsLate potentials identified in the latest isochrone of activation during sinus rhythm are infrequently correlated with successful ablation sites for VT. The targeting of slow conduction regions propagating into the latest zone of activation may be a novel and promising strategy for substrate modification.

BackgroundAccessory pathways can lie near or within the coronary sinus (CS). Radiofrequency catheter ablation of accessory pathways is a well-established treatment option, but this procedure can cause damage to adjacent coronary arteries.ObjectiveThe purpose of this study was to evaluate the anatomic relationship between the coronary arteries and the CS.MethodsRetrospective data of patients who underwent catheter ablation of supraventricular tachycardia between June 2011 and August 2013 was reviewed. In addition, detailed analysis of coronary computed tomographic angiography (CTA) data from 50 patients was performed.ResultsBetween June 2011 and August 2013, 427 patients underwent catheter ablation of supraventricular tachycardia, of whom 105 (age 28 ± 17 years, 60% male) had accessory pathway-mediated tachycardia. Of these, 23 patients had accessory pathways near the CS, and 60% (N = 14) underwent concurrent coronary angiography. In 4 patients, the posterolateral (inferolateral) branch (PLA) of the right coronary artery was in close proximity to the CS, and 2 patients (18%) had stenosis of the PLA at the site of ablation. On CTA at their closest proximity, the PLA was 1.9 ± 1.3 mm and the left circumflex artery (LCx) was 2.0 ± 0.8 mm from the body of the CS, in right and left coronary artery-dominant patients, respectively. CS ostium and PLA were 3.6 ± 1.9 mm apart. In left-dominant patients, LCx and CS ostium were 3.8 ± 1.2 mm apart.ConclusionThe PLA and LCx are in close proximity to the anteroinferior aspect of the CS ostium and proximal CS. The relationship of the CS and coronary arteries should be evaluated before ablation at these sites.

BackgroundAblation has become an important option for treatment of ventricular tachycardia (VT). The influence of procedure duration on outcomes remains unexamined.ObjectiveThe purpose of this study was to determine the influence of procedure duration on outcomes and complications over an 8-year periodMethodsPatients referred for scar-mediated VT ablation from 2004 to 2011 were retrospectively analyzed. Procedure duration was defined as the time from the insertion of catheters through the femoral vein to the time of their withdrawal. Procedure duration was analyzed in relationship with baseline and intraoperative covariates, acute procedural outcomes, complications, and 6-month clinical outcomes.ResultsOne hundred forty-eight patients underwent VT ablation with mean procedure duration of 5.7 ± 1.8 hours. VT recurrence and survival at 6 months were 46% and 82%, respectively, and were not associated with procedure duration. Hospital mortality increased with intraoperative intraaortic balloon pump insertion (adjusted odds ratio [OR] 13.7, 95% confidence interval [CI] 2.35-79.94, P = .004) and was improved with successful ablation of the clinical VT as a procedural end-point (adjusted OR 0.13, 95% Cl 0.03-0.54, P = .005). The association between procedure duration and hospital mortality remained after adjusting for significant baseline variables (adjusted OR 1.75, 95% CI 1.14-2.68, P = .0098) and intraoperative variables (adjusted OR 1.6, 95% CI 1.12-2.29, P = .0104).ConclusionHospital mortality was significantly increased by unsuccessful clinical VT ablation as a procedural end-point and intraoperative intraaortic balloon pump insertion. However, after adjusting for significant baseline and intraoperative covariates, procedure duration still was associated with increased hospital mortality. Procedure duration had no impact on VT recurrence and survival at 6 months.

Atrial fibrillation (AF) is the most common arrhythmia prompting clinical presentation, is associated with significant morbidity and mortality. The incidence and prevalence of this arrhythmia is expected to grow significantly in the coming decades. Of the available pharmacologic and non-pharmacologic treatment options, the fastest growing and most intensely studied is catheter-based ablation therapy for AF. Given the varying success rates for AF ablation, the increasingly complex factors that need to be taken into account when deciding to proceed with ablation, as well as varying definitions of procedural success, accurate detection of arrhythmia recurrence and its burden is of significance. Detecting and monitoring AF recurrence following catheter ablation is therefore an important consideration. Multiple studies have demonstrated the close relationship between the intensity of rhythm monitoring with wearable ambulatory cardiac monitors, or implantable cardiac rhythm monitors and the detection of arrhythmia recurrence. Other studies have employed algorithms dependent on intensive monitoring and arrhythmia detection in the decision tree on whether to proceed with repeat ablation or medical therapy. In this review, we discuss these considerations, types of monitoring devices, and implications for monitoring AF recurrence following catheter ablation.